Summer - United States Special Operations Command

of the X chromosome. Notable is that more than 400 millionpeople carry a G6PD-deficient gene. 1,2,3 Although dispersedworldwide, G6PD deficiency occurs with increased frequencythroughout Africa, Asia, the Middle East, and the Mediterraneanregion. While G6PD deficiency may provide a biologicaladvantage through relative resistance to Plasmodiumfalciparum malaria, it has over 440 known genetic variantsthat result in varying degrees of enzymopathy and a wide spectrumof clinical outcomes ranging from asymptomatic to severehemolytic reactions resulting in transfusion or death. 1,2G6PD deficiency has conventionally been the archetype of enzymopathyhemolytic anemias and is a leading model of hemolyticanemia resulting from intracorpuscular andextracorpuscular interaction, as most of these hemolytic casesare triggered by an exogenous agent. These exogenous triggersinclude infections, toxins, foodstuffs (ie, fava beans), andmedications (ie, antimicrobials).Although the antimicrobial primaquine prompted thediscovery of G6PD deficiency over 50 years ago, 1 primaquinecontinues to be an important adjunct used routinely for antimalarialtherapy. As a response to frequent deployments ofnumerous Army personnel to malaria-endemic regions includingAfghanistan, the Department of the Army directed thatall deploying U.S. Army personnel would undergo G6PD deficiencyscreening in order to safeguard against hemolytic reactionsresulting from primaquine therapy. 6 In this case report,it is uncertain how the individual described did not receivescreening for G6PD deficiency prior to the initiation of primaquinetherapy.By itself, primaquine is a cause of increased levels ofmethemoglobin in many patients who take it, but the levelsachieved seldom cause symptoms. However, pathologicmethemoglobinemia and hemolytic anemia do routinely occurin G6PD-deficient individuals who consume primaquine. Primaquineis known to be associated with visual accommodationcomplaints, although a review of the literature does notreveal documentation of other visual disorders to includeCRVO. However, the finding of increased erythrocyte aggregationand erythrocyte-endothelium interaction observed inhemolytic disease states may contribute to diffuse microvascularthrombosis in various organ systems to include the eye. 7Central Retinal Vein OcclusionRetinal vein occlusion includes branch retinal vein occlusionand central retinal vein occlusion. Following diabeticretinopathy, retinal vein occlusion is the second most commonsight-threatening retinal vascular disorder. The prevalence ofCRVO in the United States has been reported to be 1 per 1000and is slightly more common in men than in women. 5The majority of people diagnosed with CRVO areover the age of 50. The most common symptom of CRVO isacute and persistent monocular visual loss. Patients characteristicallypresent with an abrupt, painless, unilateral loss ofvision of variable severity. CRVO is generally categorized asischemic or nonischemic. The hallmark fundus finding ofCRVO is four-quadrant retinal hemorrhage. The more commonnonischemic form has good perfusion to the retina andrelatively good visual acuity on presentation. Vision may returnto normal if not decreased by persistent macular edema.Nonischemic CRVO can progress to ischemic CRVO, withone-third of nonischemic cases progressing to ischemic withina year. Frequent follow-up is needed to monitor for thischange. Patients can also have ischemic CRVO on initial presentationwith visual acuity typically 20/400 or worse. IschemicCRVO typically presents with more extensive retinal hemorrhage,cotton wool spots, disc edema, and often an afferentpupillary defect. Intravenous fluorescein angiogram is commonlyused to help define the level of retinal non-perfusion inCRVO. Vision loss in ischemic CRVO may result from ganglioncell ischemia, macular edema, or neovascular complicationswith secondary glaucoma.Although CRVO can occur without a known underlyingcause, it is often associated with systemic disease (atherosclerosis,autoimmune disease, diabetes, hypertension,intravenous drug abuse, renal insufficiency, tobacco use, vasculitis)or local pathology (ocular trauma, orbital abscess, orbitaltumor, glaucoma). 5,8 When CRVO occurs in youngerpatients it is often associated with blood dyscrasias such as coagulationdisorders and hyperviscosity syndromes.Sickle cell disease has been associated with a hypercoagulablestate. 7 Given the hyperviscosity and vaso-occlusivetendencies of individuals with sickle cell crisis, 9 it isinteresting that only one case of CRVO in a sickle cell patienthas been reported in the literature. 10 Additionally, it is notablethat in this sickle cell case report, a comorbid protein S deficiencymay have contributed to the ultimate CRVO pathogenesis.Furthermore, an extensive review of the medicalliterature also detected only one article describing CRVO incidencein G6PD-deficient patients. 4 However, this article postulatedprotection against CRVO in Sardinian G6PD-deficientpatients with the Mediterranean variant. The investigators inthis study cited a 3.55% incidence of CRVO in their G6PDdeficientpopulation versus a 10-15% incidence of CRVO intheir general population. Not stated in this article was the riskof CRVO development in a G6PD-deficient individual with anactive oxidative stressor.Treatment of CRVO has historically been directed towardthe management of the contributing or associated systemicmedical problem, as few treatments have had provenefficacy in the treatment of CRVO. Treatment options includeaspirin, non-steroidal anti-inflammatory drugs, plasmapheresis,anticoagulation, fibrinolytics, and systemic corticosteroids.Anti-platelet agents are frequently prescribed; however, theirefficacy is controversial. Panretinal photocoagulation is usedfor patients experiencing neovascular complications to reduceor reverse angiogenesis and avoid the development of neovascularglaucoma.Additional treatment options with improved efficacyhave recently become available. Intravitreal triamcinolone hasproven effective in reducing edema and improving vision forpatients with macular edema, 11,12 and is more likely to be efficaciousin patients without ischemic CRVO or diabetes. However,these patients sometimes have rebound symptoms andrequire continued treatment.A new approach to treating CRVO is the use of intravitrealbevacizumab. 13 Elevated levels of vascular endothelialgrowth factor (VEGF) have been found in CRVO andhave been positively correlated with the onset and progressionPreviously Published 61